Acalabrutinib in CNSL

Inclusion Criteria: * Participants must be able to understand and willing to sign a written informed consent document. * Participant must have signed and dated an IRB/IEC approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol-related procedures that are not part of normal subject care. * Participant must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests, and other requirements of the study. * Participants must be at least 18 years old on day of signing informed consent. * Participants must have a ECOG Performance Status 0-1 (see Appendix A). * Life expectancy of \> 3 months (in the opinion of the investigator). * Participants with recurrent or refractory (R/R) must have histologically confirmed DLBCL CNS lymphoma (from brain biopsy, CSF or vitreous biopsy for PCNSL/PVRL, and includes PCNSL and SCNSL) for Phase I; R/R histologically confirmed DLBCL PCNSL (from brain biopsy only) for Phase II. Participants must have received at least 1 line of CNS-directed prior therapy. There is no maximum limit on the number of prior therapies. * Confirmation of availability of sufficient tissue from brain biopsy for correlative studies is required prior to enrollment (for phase II only). The following amount of archived tissue is required: At least 10 but up to 20 unstained formalin-fixed, paraffin-embedded (FFPE) slides. Histologically confirmed …